TY - JOUR
T1 - The Genetics of Alcohol Dependence: Twin and SNP-Based Heritability, and Genome-Wide Association Study Based on AUDIT Scores
AU - Mbarek, H.
AU - Milaneschi, Y.
AU - Fedko, I.O.
AU - Hottenga, J.J.
AU - de Moor, M.H.M.
AU - Jansen, R.
AU - Gelernter, J.
AU - Sherva, R.
AU - Willemsen, G.
AU - Boomsma, D.I.
AU - Penninx, B.W.J.H.
AU - Vink, J.M.
PY - 2015
Y1 - 2015
N2 - Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE=0.12, P=0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P=7.58×10
AB - Alcohol dependence (AD) is among the most common and costly public health problems contributing to morbidity and mortality throughout the world. In this study, we investigate the genetic basis of AD in a Dutch population using data from the Netherlands Twin Register (NTR) and the Netherlands Study of Depression and Anxiety (NESDA). The presence of AD was ascertained via the Alcohol Use Disorders Identification Test (AUDIT) applying cut-offs with good specificity and sensitivity in identifying those at risk for AD. Twin-based heritability of AD-AUDIT was estimated using structural equation modeling of data in 7,694 MZ and DZ twin pairs. Variance in AD-AUDIT explained by all SNPs was estimated with genome-wide complex trait analysis (GCTA). A genome-wide association study (GWAS) was performed in 7,842 subjects. GWAS SNP effect concordance analysis was performed between our GWAS and a recent AD GWAS using DSM-IV diagnosis. The twin-based heritability of AD-AUDIT was estimated at 60% (55-69%). GCTA showed that common SNPs jointly capture 33% (SE=0.12, P=0.002) of this heritability. In the GWAS, the top hits were positioned within four regions (4q31.1, 2p16.1, 6q25.1, 7p14.1) with the strongest association detected for rs55768019 (P=7.58×10
U2 - 10.1002/ajmg.b.32379
DO - 10.1002/ajmg.b.32379
M3 - Article
SN - 1552-4841
VL - 168
SP - 739
EP - 748
JO - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
JF - American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
IS - 8
ER -
